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Preparation of Drug Carriers with Dual Redox-responsibility
via Multicomponent Polymerization of Alkynes- ACTA POLYMERICA SINICA Vol. 52, Issue 10, Pages: 1298-1307(2021)
- 作者机构：
大连理工大学化工学院 大连 116023
- 作者简介：
Nan Zheng, E-mail: nzheng@dlut.edu.cn
- 基金信息：
DOI：10.11777/j.issn1000-3304.2021.21054
CLC：Published：20 October 2021，
Published Online：11 August 2021，
Received：22 February 2021，
Revised：30 April 2021，
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何俊男,郑玉斌,郑楠.基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体[J].高分子学报,2021,52(10):1298-1307.
He Jun-nan,Zheng Yu-bin,Zheng Nan.Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes[J].ACTA POLYMERICA SINICA,2021,52(10):1298-1307.
何俊男,郑玉斌,郑楠.基于炔烃参与的多组分聚合构建氧化还原双重响应型高分子药物载体[J].高分子学报,2021,52(10):1298-1307. DOI： 10.11777/j.issn1000-3304.2021.21054.
He Jun-nan,Zheng Yu-bin,Zheng Nan.Preparation of Drug Carriers with Dual Redox-responsibility via Multicomponent Polymerization of Alkynes[J].ACTA POLYMERICA SINICA,2021,52(10):1298-1307. DOI： 10.11777/j.issn1000-3304.2021.21054.
摘要
为了拓展多组分聚合方法在药物载体领域应用，基于铜催化的炔烃多组分聚合设计合成含有二硒键的氧化还原响应型两亲性聚合物，与阿霉素(DOX)在水溶液中通过自组装方式构建纳米载药胶束. 通过实验技术手段对纳米载药胶束表征可知，纳米载药胶束的粒径在130 nm左右，临界胶束浓度(CMC)值为0.23 mg/mL，在人体正常生理条件下结构稳定. 肿瘤中含有浓度较高的活性氧(ROS)或谷胱甘肽(GSH)，聚合物主链中二硒键在氧化还原条件下断裂，导致聚合物降解，DOX从纳米载药胶束中逐渐释放，且累积释放量可达100%，并发现该类载药胶束在GSH环境中药物释放性能优于ROS环境. 该工作通过多组分聚合方式可以便捷构建氧化还原双重响应型的两亲性聚合物，在肿瘤微环境中表现出特异的降解性能，为开发设计智能响应型高分子药物载体提供新的思路.
Abstract
Multicomponent polymerization (MCP) has the advantages of high reaction efficiency
mild reaction conditions
high atomic economy and facile operation
which is a new trend in constructing complex and functional polymers. In order to explore the application of MCP in the design of drug delivery carriers
in this work
a dual redox-responsive amphiphilic polymer containing diselenide bonds was synthesized based on copper-catalyzed MCP. Amphiphilic polymer and doxorubicin (DOX) were used to construct drug-loaded nano micelles through self-assembly in aqueous solution. The characterization of the micelles shows that the particle size is about 130 nm
and the critical micelle concentration (CMC) value is 0.23 mg/mL. Under normal physiological conditions
the nano micelles remain structurally stable. However
in a tumor environment containing reactive oxygen species (ROS) or glutathione (GSH)
DOX is released from the nano drug-loaded micelles
and the cumulative release amount of DOX reaches 100%. The main reason for this result is that the diselenide bond in the polymer backbone is cleaved under redox conditions. It is found that nano drug-loaded micelles have better drug release performance in the GSH environment than those in the ROS environment. Studies have shown that the redox-responsive amphiphilic polymer is conveniently constructed through MCP
and the polymer exhibits specific degradation properties in the tumor microenvironment. This work provides a new idea for the development and design of intelligent nano drug-loaded micelles.
关键词
多组分聚合氧化还原型两亲性聚合物载药胶束二硒
Keywords
Multicomponent polymerizationRedoxAmphiphilic polymerDrug-loaded micellesDiselenide
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